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Author Credentials and Financial Disclosure: Dr. Vohra is an Assistant Clinical Professor of Medicine at the David Geffen School of Medicine at the University of California at Los Angeles, an emergency physician and the Director of Toxicology at Olive View-UCLA Medical Center.

All faculty and staff in a position to control the content of this CME activity have disclosed that they have no financial relationships with, or financial interests in, any commercial companies pertaining to this educational activity.

Describe the most common pharmacologic treatments for generalized anxiety disorder.

Outline demographic characteristics and common methods of self-harm of patients who attempt suicide and present to the emergency department.

Release Date: August 2008

Schizophrenia

Freedman R

N Engl J Med

2003;349(18):1738

Schizophrenia affects approximately one percent of all people, and is frequently encountered in the emergency department. The disease, which seems to have genetic and environmental origins, is a disorder of information processing. Hallucinations and paranoia result from an inability to distinguish extraneous stimuli from internally generated thoughts. The brain's ability to sort information by significance or accuracy is diminished, resulting in increased vulnerability to hypervigilance and social withdrawal. The stream of unsuppressed internal stimuli also contributes to perceptual and memory difficulties and other types of cognitive dysfunction.

The brain of a schizophrenic patient demonstrates aberrations in pathways for dopamine, norepinephrine, serotonin, gamma-aminobutyric acid, and acetylcholine. Similar anomalies in neurotransmission explain the delirium generated by certain psychoactive substances. Methamphetamine, which enhances dopamine and norepinephrine activity, can lead to paranoia and hallucinations due to overexcitation of the cerebral cortex. Atropine and related antimuscarinic agents induce a functional blockade of acetylcholine pathways, which also increases excitatory glutamate transmission in the cortex. These molecular disturbances can induce an agitated, psychotic state resembling the more permanent dysfunction seen with schizophrenia.

The American Psychiatric Association diagnoses schizophrenia as social and interpersonal dysfunction with at least two of these symptoms for one month or longer: delusions, hallucinations, disorganized speech, disorganized or catatonic behavior, or affective flattening. These criteria should be applied once medical illness, substance abuse, developmental disorders, and schizoaffective/bipolar disorder have been excluded.

Antipsychotic medications (also known as neuroleptics) can be broadly divided into two classes, first-generation (or typical) drugs and second-generation (or atypical) drugs. The major mechanism of first-generation antipychotics is a blockade of D2 dopamine receptors with subsequent attenuation of cortical hyperactivity. The most common effects are the Parkinsonian characteristics of slow movements, tremors, and dystonia, which typically respond to low doses of anticholinergic medications such as Benadryl or Cogentin. Akathisia, a feeling of inner restlessness which can resemble agitation, can be controlled with propranolol or sedatives. After several years of therapy, about one-third of patients develop tardive dyskinesia, a potentially irreversible syndrome of complex involuntary gestures often in the hands and face.

The most serious acute adverse effect of antipsychotic therapy is neuroleptic malignant syndrome (NMS), a severe dysregulation of body temperature, mentation, and motor tone. Hyperthermia, confusion, and diffuse “lead-pipe” rigidity are the classic criteria for diagnosing NMS. In the emergency department, it is often difficult to distinguish this condition from other life-threatening conditions such as meningitis, thyroid storm, heat stroke, and sympathomimetic stimulant overdose. Treatment is focused on aggressive cooling and hydration measures, bromocriptine (a dopamine agonist), and avoiding anticholinergic drugs because these agents block perspiration.

Chlorpromazine is a prototypical example of a first-generation antipsychotic. Other agents such as haloperidol are more potent dopamine blockers, but are also more likely to cause extrapyramidal side effects. About 20 percent of patients have complete remission of symptoms after first-generation antipsychotic drugs are initiated, but the majority of patients have a partial response.

An important cardiovascular side effect of antipsychotic agents in therapeutic doses and overdoses is prolongation of the QT interval. Thioridizine is especially notorious for inducing this abnormality, which can predispose to multifocal ventricular tachycardia (Torsades de Pointes). The incidence of sudden cardiac death in patients on antipsychotic medications is about twice the average rate.

Second-degree antipsychotics include clozapine, risperidone, olanzapine, quetiapine, and ziprasidone. These agents affect dopaminergic and serotonergic pathways resulting in greater efficacy and decreased extrapyramidal symptoms, although they also cause more weight gain. Clozapine, one of the most effective second-generation antipsychotics, is associated with severe agranulocytosis, myocarditis, lens opacities, hypersalivation, and seizures.

If a patient with symptoms of schizophrenia requires initiation of treatment in the emergency department, a second-generation antipsychotic (other than clozapine) should be initiated, with the expectation of improvement in symptoms within several days. First-generation agents and clozapine should be considered second- and third-line regimens if other options prove unsuccessful. Depot regimens of first-generation drugs are a suitable alternative if poor compliance is an issue. It is also important to recognize that, as with treatment of depression, there is a paradoxical increase in risk of death as the patient's other symptoms improve.

Generalized Anxiety Disorder

Fricchione G

N Engl J Med

2004;351(7):675

With a lifetime prevalence of five percent, anxiety disorders are the most prevalent psychiatric condition in the United States besides disorders of substance abuse. The subject of this clinical vignette is Generalized Anxiety Disorder (GAD). The diagnostic criteria for GAD include excessive anxiety and worry about a variety of events and activities occurring most days for six months. As with other psychiatric diagnoses, it is important to rule out medical conditions that mimic GAD such as cardiopulmonary disease, thyroid and other endocrine disorders, sedative or alcohol withdrawal, and the use of exogenous substances such as stimulants, herbal remedies, steroids, cold medications, and excessive caffeine.

An important coexisting mental illness is major depression, with two-thirds of GAD patients having both diagnoses. GAD also can occur in association with panic attacks, obsessive-compulsive disorder, post-traumatic stress disorder (PTSD), social phobia, and somatization disorder. Patients with GAD and depression or another medical condition are at increased risk of suicide, and it is important to ask about suicidal thoughts or plans during ED assessment.

Therapy for anxiety disorder can be initiated in the ED using a variety of medications, such as benzodiazepines, newer antidepressant medications, and other anxiolytic agents. Benzodiazepines are effective in initiating acute treatment of GAD, but may be limiting as chronic agents because of the potential for physical dependence and excessive sedation. Selective serotonin reuptake inhibitors (e.g., paroxetine) and serotonin-norepinephrine reuptake inhibitors (e.g., venlafaxine) are effective, FDA-approved agents for treatment of GAD and depression, and typical courses of treatment range from eight weeks to six months. Combining benzodiazepines with antidepressant agents seems to be an effective approach for therapy, probably because so many patients have a combination of depression and anxiety. Another alternative is buspirone, a non-benzodiazepine anxiolytic agent that does not cause sedation, physical dependence, or withdrawal. Buspirone is also considered safer in pregnancy than benzodiazepines, which are associated with an increased risk of oral clefts, neonatal hypotonia, and postpartum withdrawal. Psychotherapy also can be quite effective for reducing anxiety symptoms.

National Study of U.S. Emergency Department Visits for Attempted Suicide and Self-Inflicted Injury, 1997–2001

Doshi A, et al

Ann Emerg Med

2005;46(4):369

Self-inflicted injury is a tragic and common problem in many emergency departments. In this article, data were collected from the CDC's National Hospital Ambulatory Medical Care Survey, which samples patient data yearly from approximately 400 emergency departments nationwide. Although federal, military, and Veterans Affairs hospitals are excluded from this survey, it provides some interesting demographic information about ED patients with self-inflicted injuries.

The total number of ED visits for self-inflicted injury is estimated to be 412,000 per year. During the five-year study period (1997–2001), attempted suicide accounted for 0.4 percent of all ED visits. The mean patient age was 31, but adolescents 15 to 19 have double the average rate of other age groups. There was no difference in rates by region. The most common method of injury was poisoning (68%), followed by cutting or piercing (20%).

Eighty percent of poisonings were from ingestions of unspecified prescription medicines, sedating or psychiatric agents, analgesics, or antipyretics, although the article did not provide details. A third of patients were admitted to the hospital, and a third of those were admitted to the ICU. An underlying psychiatric disorder was described for more than half of patients, and alcohol abuse was described in 16 percent. The peak hours of presentation were between 6 p.m. and midnight.

These statistics help clarify the demographic details of patients who attempt suicide, a population different from those that actually complete it. Those attempting suicide tend to be younger and more evenly divided by gender, but those committing suicide tend to be older, single, male, alcoholic, and chronically physically ill. Because attempted suicide is a significant risk factor for successful completion on a subsequent attempt, this study provides a useful foundation for ED-based interventions aimed at reducing suicide deaths.

About the LLSA

As part of its continuous certification program, the American Board of Emergency Medicine has developed the Lifelong Learning and Self-Assessment (LLSA) program to promote continuous education of diplomates. Each year, beginning in 2004, 16 to 20 articles are chosen based on the Emergency Medicine Model. A list of these articles can be found on the ABEM web site, www.abem.org.

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